Phosphoinositide 3-kinases (PI3Ks) are an evolutionary conserved family of lipid kinases that control cell growth, metabolism and survival. By generating lipid second messengers that interact with specialized lipid-binding domains found in a wide spectrum of signaling molecules, PI3Ks instigate signaling through a network of downstream effector pathways. Genetic studies in zebrafish and mice revealed the critical importance of intact PI3K signaling in the endothelium and provided first insights into how individual PI3K isoforms are utilized to control vascular development and function. Here, we review the myriad roles of PI3Ks in the endothelium and the mechanisms through which they couple environmental signals with specific steps of angiogenic vessel growth.
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